A gene-amplification model of carcinogenesis, recently publiched by the principal investigator, proposes that the initial event in the process (initiation) is the induction of a large tandem duplication. The model predicts that large tandem duplications will be induced by carcinogens and that carcinogens may be detected using genetic systems with specifically select for such duplications. We propose here to develop a system in Salmonella typhimurium which can be used to test both of these prediction and can also be used as a mutagen-carcinogen screening system to detect previously unidentified carcinogens. The proposed tester system should be a better predictor of carcinogenic activity of different chemical than other screening systems, if the gene-amplification model is correct, because it is testing for the specific type of genetic change involved in carcinogenesis. Preliminary evidence supporting the use of the proposed model system is presented. The system can also be used to probe the mechanism of tandem duplication induction. The proposed tandem duplication system is uniquely attractive because: 1. Available evidence indicates that the selection procedure used will select specifically for tandem duplications. 2. Various strains can be easily constructed to take advantage of genetic backgrounds previously shown to be useful for carcinogen testing (uvrB, rfa, pKM101 etc.). 3. Other techniques developed for the Salmonella system such as use of rat liver microsome metabolism of potential carcinogens and host mediated assays should also be applicable.